Process for preparing pesticidal intermediates

ABSTRACT

A process for preparing pesticides or pesticidal intermediates, particularly 5-amino-1 aryl-3-cyanopyrazoles, having the formula  
                 
 
said process comprising reacting a compound having the formula  
                 
with a cyanide salt.

This application is a divisional of application Ser. No. 09/890,653,filed Nov. 2, 2001, now allowed, incorporated by reference herein in itsentirety and relied upon, which is the U.S. national phase ofInternational Application No. PCT/EP00/01 101, filed Feb. 1, 2000, andpublished in English on Aug. 10, 2000 under Publication No. WO 00/46210.

This invention relates to novel processes for preparing pesticides orpesticidal intermediates particularly 5-amino-1-aryl-3-cyanopyrazolederivatives).

European Patent Publication Nos. 0295117 and 0234119 describe thepreparation of pesticidally active phenylpyrazole compounds and of5-amino-1-aryl-3-cyanopyrazole intermediate compounds used in theirsynthesis.

Various methods for preparing these compounds are known. The presentinvention seeks to provide improved or more economical methods for thepreparation of pesticides and the intermediate compounds useful inpreparing them.

It is a first object of the present invention to provide a convenientprocess for preparing pesticidally active phenylpyrazole compounds or5-amino-1-aryl-3-cyanopyrazole pesticidal intermediates, which areobtained in high yield and high purity.

It is a second object of the present invention to provide a convenientprocess for preparing pesticidally active phenylpyrazole compounds or5-amino-1-aryl-3-cyanopyrazole pesticidal intermediates, which proceedswithout the need for a diazotization step and hence avoids problems suchas hazards known to occur for such reactions.

It is a third object of the present invention to provide a process forpreparing pesticidally active phenylpyrazole compounds or5-amino-1-aryl-3-cyanopyrazole pesticidal intermediates, which is simpleto perform and uses less expensive starting materials than knownmethods.

It is a still further object of the present invention to provide novelintermediates in the manufacture of pesticidally active compounds.

These and other objects of the invention will become apparent from thefollowing description, and are achieved in whole or in part by thepresent invention.

The present invention accordingly provides a process (A) for thepreparation of a compound of formula (I):

wherein W represents nitrogen or —CR⁴

-   -   R¹ represents halogen, haloalkyl (preferably trifluoromethyl),        haloalkoxy (preferably trifluoromethoxy), R⁵S(O)_(n)—, or —SF₅;    -   R² represents hydrogen or halogen (for example chlorine or        bromine);    -   R³ represents hydrogen or R⁶S(O)_(m)—;    -   R⁴ represents halogen (for example chlorine or bromine);    -   R⁵ and R⁶ represent alkyl or haloalkyl; and    -   m and n represent 0, 1 or 2; which process comprises the        reaction of a compound of formula (II):        wherein R¹, R², R³ and W are as hereinabefore defined, R⁷        represents a leaving group (preferably chlorine or bromine) and        R⁸ represents chlorine or bromine (preferably R⁷ and R⁸ each        represent chlorine), with a cyanide salt. The reaction proceeds        via dicyano intermediates of formula (III):        wherein R¹, R², R³ and W are as hereinbefore defined, which        generally cyclize under the conditions of the reaction, thus        providing a simple and convenient process. Optionally the        intermediates of formula (III) may be cyclized in the presence        of base according to known methods. Compounds of formula (II)        and (III) may exist as a mixture of syn and anti isomers.

Unless otherwise specified in the present specification ‘alkyl’ meansstraight- or branched-chain alkyl having from one to six carbon atoms(preferably one to three). Unless otherwise specified ‘haloalkyl’ and‘haloalkoxy’ are straight- or branched-chain alkyl or alkoxyrespectively having from one to six carbon atoms (preferably one tothree) substituted by one or more halogen atoms selected from fluorine,chlorine or bromine.

Suitable cyanide salts for the above reaction to form compounds offormula (I) include alkali metal cyanides such as potassium, sodium orlithium cyanide, alkaline earth metal cyanides or ammonium cyanide.Potassium cyanide or sodium cyanide are preferred. The reaction isgenerally conducted in a solvent. Solvents suitable for use includenitrites such as acetonitrile, amides such as N-methylpyrrolidinone,sulfoxides such as dimethylsulfoxide, ethers such as tetrahydrofuran oralcohols such as ethanol. Water may be employed as a co-solvent. Thereaction temperature is generally from about −20° C. to the refluxtemperature of the solvent, and preferably from about 0° C. to about 20°C.

Generally from two to 5 molar equivalents of cyanide and preferably fromabout two to about three equivalents are employed.

In formulae (I), (II) and (III) and in the formulae depictedhereinafter, preferred values of the symbols are as follows:-

-   -   R¹ represents haloalkyl (preferably trifluoromethyl), haloalkoxy        (preferably trifluoromethoxy) or —SF₅;    -   W represents —CR⁴;    -   R² and R⁴ represent halogen (preferably chlorine);    -   R³ represents a hydrogen atom, or R⁶S(O)_(m)—;        wherein R⁶ represents optionally halogenated methyl or ethyl        (preferably trifluoromethyl); and R⁷ and R⁸ represents chlorine.

Particularly preferred compounds of formula (I) include:

-   -   5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole;    -   5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylthiopyrazole;    -   5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylsulfmylpyrazole;        and    -   5        amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-ethylsulfinylpyrazole.

The process is particularly useful for preparing compounds in which R³represents hydrogen, and most preferably for5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole.

In formulae (II) and (III) and in the formulae depicted hereinafter, themost preferred values of the symbols are as follows:-

-   -   R¹ represents trifluoromethyl;    -   W represents —CR⁴;    -   R², R⁴, R⁷ and R⁸ represent chlorine; and    -   R³ represents hydrogen.

According to a further feature of the present invention the aboveprocess (A) can be combined with additional process steps (B) and (C) asdefined hereinbelow.

Process step (B) comprises the reaction of a compound of formula (IV):

wherein R¹, R², R³, R⁷ and W are as hereinbefore defined, with achlorinating or brominating agent; to give a compound of formula (II)wherein R¹, R², R³, R⁷ and R⁸ and W are as hereinbefore defined.

Suitable chlorinating agents are thionyl chloride, phosphoryl chloride,phosphorus trichloride, phosphorus pentachloride or a mixture oftriphenylphosphine and carbon tetrachloride. Brominating agents whichmay be used include thionyl bromide, phosphoryl bromide or a mixture oftriphenylphosphine and carbon tetrabromide. Preferably the process isperformed using a chlorinating agent. A preferred chlorinating agent isphosphoryl chloride.

Solvents which may be used include ethers, aromatic hydrocarbons such astoluene, aromatic halogenated hydrocarbons such as chlorobenzene, orhalogenated hydrocarbons such as dichloroethane.

The reaction temperature is generally from 0° C. to 120° C., preferablyfrom 70° C. to 90° C.

Process step (C) comprises the reaction of an arylhydrazine compound offormula (V):

wherein R¹, R² and W are as hereinbefore defined; with a compound offormula (VI):R³R⁷CHCOR⁹   (VI)wherein R³ and R⁷ are as defined above, and R⁹ represents a leavinggroup preferably a chlorine or bromine atom (generally both R⁷ and R⁹represent a chlorine atom); to give a compound of formula (IV) asdefined above. The reaction to obtain compounds of formula (IV) isgenerally performed in a solvent such as halogenated hydrocarbons forexample dichloroethane, ethers for example tetrahydrofuran or dioxan, orN,N-dialkylamides for example N,N-dimethylformamide, and at atemperature of from −20° C. to 50° C., preferably from 0 to 20° C.

The above combination of process step (A), preceded by process step (B),preceded by process step (C), represents in certain aspects animprovement over the prior art.

Compounds of formula (II) and (IV) above are novel and thereforeconstitute a further feature of the present invention.

Where R³ is other than hydrogen, compounds of formula (III) are novel.

Compounds of formula (VI) are known.

The intermediate 5-amino-1-aryl-3-cyanopyrazole compounds of formula (I)obtained by the process (A) of the invention wherein R representshydrogen, may be used in the preparation of pesticidally activephenylpyrazole derivatives of formula (VI) according to the followingreaction scheme:

wherein the symbols used above are as hereinbefore defined.

The following non-limiting examples illustrate the invention. NMRspectra are recorded using deuterochloroform as solvent.

EXAMPLE 1 Preparation of5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-cyanopyrazole

A solution ofN′-(2,6-dichloro-4-trifluoromethylphenyl)-chloroacetohydrazonoylchloride (1.1 g) in ethanol (6 ml) was added during 25 minutes to astirred solution of sodium cyanide (0.475 g) in ethanol (6 ml) and water(6 ml). The temperature rose to 32° C. After 15 minutes an addition ofethanol (4.5 ml) and water (3 ml) was made and stirred for 15 minutes at20° C. A further addition of water (3 ml) was made and the mixturefiltered. The residue was dissolved in ethanol, concentrated andpurified by chromatography on silica gel eluting with dichloromethane togive the title compound (0.55 g), obtained in 53% yield.

EXAMPLE 2 Preparation ofN′-(2,6-dichloro-4-trifluoromethylphenyl)-chloroacetohydrazonoylchloride

Phosphoryl chloride (500 microlitres, 1.7 equivalents) was added in oneportion to a stirred solution ofN′-(2,6-dichloro-4-trifluoromethylphenyl)-chloroacetohydrazide (1.0 g,3.11 mmol) in toluene (20 ml) and heated at 70° C. under an argonatmosphere for 20 hours. The cooled mixture was evaporated and theresidue extracted with cyclohexane. The extracts were combined andevaporated to give the title compound (0.971 g) as an orange oil, NMR4.4(s,2H), 7.55(s,2H), 7.7(s,1H). The yield was 90%.

EXAMPLE 3 Preparation ofN′-(2,6-dichloro-4-trifluoromethylphenyl)-chloroacetohydrazide

A solution of chloroacetyl chloride (2.3 ml, 1.08 equivalents) inanhydrous dichloromethane (30 ml) was added during 30 minutes to astirred solution of 2,6-dichloro-4-trifluoromethylphenylhydrazine (6.1g, 24.89 mmol) in anhydrous dichloromethane (60 ml) maintaining between5 and 12° C. under an argon atmosphere. The mixture was then stirred for5-12 hours at 20° C. A solution of sodium hydroxide (11.2 ml of 10%) anddichloromethane were added and the organic phase washed (water), dried(magnesium sulfate) and evaporated to give the title compound (7.25 g)as a white solid, NMR 4.05(s,2H), 6.77(s,1H), 7.47(s,2H), 8.6(s,1H). Theyield was 91%.

1-49. (canceled)
 50. A compound having the formula:

wherein: W is —CR⁴; R¹ is halogen, haloalkyl, haloalkoxy, R⁵S(O)_(n)— or—SF₅; R² is hydrogen or halogen; R³ is hydrogen or R⁶S(O)_(m)—; R⁴ ishalogen; each of R⁵ and R⁶ is alkyl or haloalkyl; R⁷ is a leaving group;R⁸ is chlorine or bromine; and each of m and n is 0, 1 or
 2. 51. Acompound according to claim 50, wherein R⁷ is chlorine or bromine.
 52. Acompound according to claim 50, wherein: R¹ is trifluoromethyl,trifluoromethoxy or —SF₅; each of R² and R⁴ is chlorine or bromine; R³ishydrogen or R⁶S(O)_(m)—; R⁶ is optionally halogenated methyl or ethyl;and each of R⁷ and R⁸ is chlorine.
 53. A compound according to claim 50,wherein: R¹ is trifluoromethyl; each of R², R⁴, R⁷, and R⁸ is chlorine;and R³ is hydrogen.
 54. A compound having the formula:

wherein: W is —CR⁴; R¹ is halogen, haloalkyl, haloalkoxy, R⁵S(O)_(n)— or—SF₅; R² is hydrogen or halogen; R³is hydrogen or R⁶S(O)_(m)—; R⁴ ishalogen; each of R⁵ and R⁶ is alkyl or haloalkyl; R⁷is a leaving group;and each of m and n is 0, 1 or
 2. 55. A compound according to claim 54,wherein R⁷ is chlorine or bromine.
 56. A compound according to claim 54,wherein: R¹ is trifluoromethyl, trifluoromethoxy or —SF₅; each of R² andR⁴ is chlorine or bromine; R³ is hydrogen or R⁶S(O)_(m)—; R⁶ isoptionally halogenated methyl or ethyl; and R⁷ is chlorine.
 57. Acompound according to claim 54, wherein: R¹ is trifluoromethyl; each ofR², R⁴ and R⁷ is chlorine; and R³ is hydrogen.